Ginsenosides in hepatocellular carcinoma: preclinical evidence, mechanisms, and clinical implications

Abstract

Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality worldwide, with limited effectiveness of current strategies and persistent challenges in early detection and outcome prediction. This review summarizes the preclinical evidence supporting the therapeutic potential of ginsenosides from Panax ginseng—particularly Rh2 and Rg3—in HCC cellular and animal models. Mechanistically, the antitumor effects are discussed in relation to induction of apoptosis, modulation of autophagy and other cell-death–associated signaling, and reprogramming of the tumor microenvironment, alongside evidence for suppression of metastatic behavior and enhancement of antitumor immunity. Finally, the review provides clinical implications by highlighting how these mechanistic findings may inform future translation, including opportunities for rational combination regimens and drug delivery approaches to overcome key translational bottlenecks—particularly low bioavailability and the lack of reliable biomarkers for response prediction and patient stratification—to optimize clinical application. Overall, the available preclinical data suggest that ginsenosides are promising candidates for improving HCC management, while emphasizing the need for further mechanistically rigorous and translational studies to support clinical optimization.